1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine, also known as vortioxetine, is a multimodal serotonergic compound intended to be used in the treatment of major depressive disorder and generalized anxiety disorder. The compound shows antagonistic properties at 5-HT3A and 5-HT7 receptors, partial agonistic properties at 5-HT1B receptors, agonistic properties at 5-HT1A receptors and potent serotonin reuptake inhibition via inhibition of the serotonin transporter (SERT). 1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine is represented by the following general formula (I):

Vortioxetine free base is disclosed in WO 2003/029232 A1.
WO 2007/144005 A1 discloses crystalline vortioxetine free base, a variety of crystalline polymorphs and pseudopolymorphs of vortioxetine hydrobromide, including a hemihydrate and an ethyl acetate solvate thereof, crystalline vortioxetine hydrochloride and a monohydrate thereof, and crystalline forms of vortioxetine mesylate, hydrogenfumarate, hydrogenmaleate, mesohydrogentartrate, L-(+)-hydrogentartrate, D-(−)-hydrogentartrate, hydrogen sulphate, dihydrogenphosphate and nitrate.
WO 2010/094285 A1 discloses an isopropanol solvate of vortioxetine hydrobromide as well as a process for the purification of vortioxetine and pharmaceutically acceptable salts thereof.
WO 2010/121621 A1 discloses crystalline forms of vortioxetine L-lactate and vortioxetine DL-lactate.
However, there still remains a need for alternative solid state forms of vortioxetine with improved physicochemical properties such as e.g. improved solubility and bioavailability, low hygroscopicity, high chemical and physical stability, convenient toxicity profile, etc.
The bioavailability of a compound intended to be administered orally is dependent on the compound's solubility as well as the compound's permeability according to the biopharmaceutical classification system (BCS). Therefore a solid state form of vortioxetine having high aqueous solubility, and which is consequently highly orally bioavailable, is desirable.
In addition, an active pharmaceutical ingredient of a solid pharmaceutical formulation preferably shows low hygroscopicity in order to ensure chemical and physical quality during storage of the active substance itself and during the shelf-life of the finished dosage form containing the active substance without the need for special and expensive packaging. Hence, a solid state form of vortioxetine showing low hygroscopicity and consequently being physically and chemically stable when exposed to increased relative humidity is preferable for the preparation of a solid pharmaceutical composition.
Most preferable is a solid state form of vortioxetine combining both high aqueous solubility and low hygroscopicity suitable for the preparation of a solid pharmaceutical composition for oral administration.